Restoration of telomerase activity rescues chromosomal instability and premature aging in Terc-/- mice with short telomeres.

Reconstitution of telomerase activity is proposed as a potential gene therapy to prevent, or rescue, age-related diseases produced by critical telomere shortening. However, it is not known whether or not short telomeres are irreversibly damaged. We addressed this by re-introducing telomerase in late generation telomerase-deficient mice, Terc-/-, which have short telomeres and show severe proliferative defects.

Increased epidermal tumors and increased skin wound healing in transgenic mice overexpressing the catalytic subunit of telomerase, mTERT, in basal keratinocytes.

Telomerase transgenics are an important tool to assess the role of telomerase in cancer, as well as to evaluate the potential use of telomerase for gene therapy of age-associated diseases. Here, we have targeted the expression of the catalytic component of mouse telomerase, mTERT, to basal keratinocytes using the bovine keratin 5 promoter. These telomerase-transgenic mice are viable and show histologically normal stratified epithelia with high levels of telomerase activity and normal telomere length.

Telomerase-deficient mice with short telomeres are resistant to skin tumorigenesis.

Inhibition of telomerase is proposed to limit the growth of cancer cells by triggering telomere shortening and cell death. Telomere maintenance by telomerase is sufficient, in some cell types, to allow immortal growth. Telomerase has been shown to cooperate with oncogenes in transforming cultured primary human cells into neoplastic cells, suggesting that telomerase activation contributes to malignant transformation.

Characterization of a membrane-associated, receptor and G-protein responsive phosphoinositide-specific phospholipase C from avian erythrocytes.

We describe the reconstitution and purification of a membrane-associated phosphoinositide-specific phospholipase C (PIC) from turkey erythrocyte ghosts. This PIC is responsive to a G-protein coupled to P2y purinergic receptors which are expressed in turkey erythrocytes. Reconstitution is achieved by adding partially purified PIC to [3H]inositol-prelabelled turkey erythrocyte membranes depleted of their endogenous PIC (acceptor membranes).

Pathways of dephosphorylation of 1-D-myo-inositol 1,4,5-trisphosphate in GH3 pituitary tumor cells.

Previous work in [3H]inositol-labelled GH3 pituitary tumor cells stimulated with thyrotropin-releasing hormone (TRH) reported the existence of at least ten distinct [3H]inositol-containing substances which were identified as different inositol mono-, bis- and tris-phosphate isomers [1]. Here a complete kinetic study of the dephosphorylation pathways of the second messenger Ins(1,4,5)P3 is reported in GH3 cell homogenates, identifying a new intermediate, Ins(4,5)P2, in the metabolism of the second messenger. in vitro results obtained with exogenous substrates are compared with in vivo results obtained measuring levels of the endogenous [3H]inositol-labelled isomers that participate in the dephosphorylation pathways of Ins(1,4,5)P3 in resting and TRH-stimulated GH3 cells.